This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We will be determining the structures of multiple protein targets relevant to the pharmaceutical industry. This will include structures of these targets with small-molecule inhibitors bound. This work requires a tunable x-ray source, both for de novo protein structure determination and for detection of anomalous scatterers (e.g., bromine) in our small-molecule ligands. Macromolecular crystals of approximate size 100x100x50 micron will be used for experiment. This is a routine experiment using frozen protein crystals in cryoprotectant.